Abstract
BackgroundA rapid surge of female breast cancer has been observed in young women in several East Asian countries. The BIM deletion polymorphism, which confers cell resistance to apoptosis, was recently found exclusively in East Asian people with prevalence rate of 12%. We aimed to evaluate the possible role of this genetic alteration in carcinogenesis of breast cancer in East Asians.MethodFemale healthy volunteers (n = 307), patients in one consecutive stage I-III breast cancer cohort (n = 692) and one metastatic breast cancer cohort (n = 189) were evaluated. BIM wild-type and deletion alleles were separately genotyped in genomic DNAs.ResultsBoth cancer cohorts consistently showed inverse associations between the BIM deletion polymorphism and patient age (≤35 y vs. 36-50 y vs. >50 y: 29% vs. 22% vs. 15%, P = 0.006 in the consecutive cohort, and 40% vs. 23% vs. 13%, P = 0.023 in the metastatic cohort). In healthy volunteers, the frequencies of the BIM deletion polymorphism were similar (13%-14%) in all age groups. Further analyses indicated that the BIM deletion polymorphism was not associated with specific clinicopathologic features, but it was associated with poor overall survival (adjusted hazard ratio 1.71) in the consecutive cohort.Conclusions BIM deletion polymorphism may be involved in the tumorigenesis of the early-onset breast cancer among East Asians.
Highlights
The incidence of breast cancer among Asian women is in general lower than that in Western countries
Further analyses indicated that the BIM deletion polymorphism was not associated with specific clinicopathologic features, but it was associated with poor overall survival in the consecutive cohort
BIM deletion polymorphism may be involved in the tumorigenesis of the early-onset breast cancer among East Asians
Summary
The incidence of breast cancer among Asian women is in general lower than that in Western countries. Compared to Caucasian American women, the age-period-cohort analyses consistently revealed a much stronger birth cohort effect on the breast cancer incidence of Singaporean, Japanese, and Taiwanese women [1,3,4] This strong birth cohort effect correlated directly with a rapid increase in the incidence of early-onset breast cancer in these countries. Our recent study demonstrated a major discrepancy of molecular subtype distributions between Taiwanese and Caucasian YFBC In contrast to their Western counterpart, Taiwanese YFBCs are characterized by a luminal A subtype (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive and human epidermal growth factor receptor 2 [HER2] negative) prevalence, and low basal-like subtype prevalence [6].
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